Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene.
J Autoimmun
; 86: 116-119, 2018 01.
Article
en En
| MEDLINE
| ID: mdl-28942902
ABSTRACT
BACKGROUND:
Risk of autoimmune thyroid disease (AITD) is strongly heritable. Multiple genes confer increased risk for AITD, but a monogenic origin has not yet been described. We studied a family with apparent autosomal dominant, early onset Hashimoto thyroiditis.METHODS:
The family was enrolled in an IRB-approved protocol. Whole exome sequencing was used to study the proband and an affected sibling. The identified variant was studied in other family members by Sanger sequencing.RESULTS:
We identified a previously unreported splice site variant in the thyroglobulin gene (TG c.1076-1G > C). This variant was confirmed in all affected family members who underwent testing, and also noted in one unaffected child. The variant is associated with exon 9 skipping, resulting in a novel in-frame variant transcript of TG.CONCLUSION:
We discovered a monogenic form of AITD associated with a splice site variant in the thyroglobulin gene. This finding raises questions about the origins of thyroid autoimmunity; possible explanations include increased immunogenicity of the mutated protein or thyroid toxicity with secondary development of anti-thyroid antibodies. Further study into the effects of this variant on thyroid function and thyroid autoimmunity are warranted.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tiroglobulina
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Linfocitos T
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Enfermedad de Hashimoto
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Isoformas de ARN
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Proteínas de la Leche
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Mutación
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2018
Tipo del documento:
Article